CN111194221A - 优化的核酸抗体构建体 - Google Patents

优化的核酸抗体构建体 Download PDF

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Publication number
CN111194221A
CN111194221A CN201880046347.6A CN201880046347A CN111194221A CN 111194221 A CN111194221 A CN 111194221A CN 201880046347 A CN201880046347 A CN 201880046347A CN 111194221 A CN111194221 A CN 111194221A
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seq
fold
dmab
acid sequence
amino acid
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CN201880046347.6A
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Chinese (zh)
Inventor
大卫·韦纳
吉亚贝·古伊宾加
尼尔·库奇
查尔斯·里德
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Wistar Institute of Anatomy and Biology
Inovio Pharmaceuticals Inc
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Wistar Institute of Anatomy and Biology
Inovio Pharmaceuticals Inc
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    • C07K16/10Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
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    • G16B15/00ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
    • G16B15/20Protein or domain folding
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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CN201880046347.6A 2017-05-10 2018-05-10 优化的核酸抗体构建体 Pending CN111194221A (zh)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201762504460P 2017-05-10 2017-05-10
US201762504448P 2017-05-10 2017-05-10
US62/504,448 2017-05-10
US62/504,460 2017-05-10
US201862624367P 2018-01-31 2018-01-31
US201862624320P 2018-01-31 2018-01-31
US62/624,320 2018-01-31
US62/624,367 2018-01-31
PCT/US2018/032023 WO2018209055A1 (en) 2017-05-10 2018-05-10 Optimized nucleic acid antibody constructs

Publications (1)

Publication Number Publication Date
CN111194221A true CN111194221A (zh) 2020-05-22

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CN201880046347.6A Pending CN111194221A (zh) 2017-05-10 2018-05-10 优化的核酸抗体构建体

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US (1) US20210188947A1 (de)
EP (1) EP3621640A4 (de)
JP (2) JP2020519285A (de)
KR (2) KR102455340B1 (de)
CN (1) CN111194221A (de)
AU (1) AU2018265261A1 (de)
BR (1) BR112019023540A2 (de)
CA (1) CA3063051A1 (de)
MX (1) MX2019013370A (de)
WO (1) WO2018209055A1 (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110167584A (zh) * 2016-11-07 2019-08-23 威斯塔解剖学和生物学研究所 用于针对莱姆病的dna抗体构建体
CN113939533A (zh) * 2020-06-18 2022-01-14 深圳迈瑞生物医疗电子股份有限公司 抗可溶性cd14亚型抗体、试剂盒及其应用

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4137158A1 (de) 2015-08-07 2023-02-22 Imaginab, Inc. Gegen moleküle gerichtete antigenbindende konstrukte
US11230592B2 (en) * 2017-09-27 2022-01-25 The Wistar Institute Of Anatomy And Biology DNA antibody constructs for use against middle east respiratory syndrome coronavirus
US20230302120A1 (en) * 2020-08-11 2023-09-28 The Board Of Regents Of The University Of Texas System Proteins, polynucleotides, and methods for treating coronavirus infection
AU2022373303A1 (en) * 2021-10-20 2024-05-09 Memorial Hospital For Cancer And Allied Diseases Anti-tshr multi-specific antibodies and uses thereof
WO2023077061A1 (en) * 2021-10-28 2023-05-04 David Weiner Bispecific immune cell engagers targeting hiv and methods of use thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009134027A2 (en) * 2008-04-30 2009-11-05 Ajou University Industry-Academic Cooperation Foundation Anti-nucleic acid antibody inducing cell death of cancer cells and composition for preventing or treating cancers comprising the same

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8928874D0 (en) * 1989-12-21 1990-02-28 Celltech Ltd Humanised antibodies
US5858725A (en) * 1990-10-10 1999-01-12 Glaxo Wellcome Inc. Preparation of chimaeric antibodies using the recombinant PCR strategy
US6261787B1 (en) * 1996-06-03 2001-07-17 Case Western Reserve University Bifunctional molecules for delivery of therapeutics
ES2699273T3 (es) * 2006-12-01 2019-02-08 Novartis Ag Anticuerpos anti-P-selectina y métodos de uso de los mismos para tratar enfermedades inflamatorias
CN102421800A (zh) * 2009-02-23 2012-04-18 格兰马克药品股份有限公司 结合cd19的人源化抗体及其用途
JP5717624B2 (ja) * 2009-03-19 2015-05-13 中外製薬株式会社 抗体定常領域改変体
TWI588156B (zh) * 2011-03-28 2017-06-21 賽諾菲公司 具有交叉結合區定向之雙重可變區類抗體結合蛋白
EP2699688A1 (de) * 2011-04-20 2014-02-26 The Trustees Of The University Of Pennsylvania Dosierpläne und zusammensetzungen zur aav-vermittelten passiven immunisierung von luftbürtigen krankheitserregern
US9562110B2 (en) * 2012-11-21 2017-02-07 Wuhan Yzy Biopharma Co., Ltd. Bispecific antibody
SG11201604719WA (en) * 2013-12-13 2016-07-28 Univ Pennsylvania Dna antibody constructs and method of using same
EP3875481A1 (de) * 2014-11-14 2021-09-08 The U.S.A. as represented by the Secretary, Department of Health and Human Services Neutralisierende antikörper gegen ebola-virus-glycoprotein und deren verwendung
WO2016145385A2 (en) * 2015-03-11 2016-09-15 Integrated Biotherapeutics, Inc. Pan-ebola and pan-filovirus protective epitopes, antibodies, and antibody cocktails
EP3344295B1 (de) * 2015-08-31 2022-02-23 Helixmith Co., Ltd. Chimäre anti-sialyl-tn-antigenrezeptoren

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009134027A2 (en) * 2008-04-30 2009-11-05 Ajou University Industry-Academic Cooperation Foundation Anti-nucleic acid antibody inducing cell death of cancer cells and composition for preventing or treating cancers comprising the same

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110167584A (zh) * 2016-11-07 2019-08-23 威斯塔解剖学和生物学研究所 用于针对莱姆病的dna抗体构建体
CN110167584B (zh) * 2016-11-07 2024-06-07 威斯塔解剖学和生物学研究所 用于针对莱姆病的dna抗体构建体
CN113939533A (zh) * 2020-06-18 2022-01-14 深圳迈瑞生物医疗电子股份有限公司 抗可溶性cd14亚型抗体、试剂盒及其应用

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EP3621640A4 (de) 2021-06-30
BR112019023540A2 (pt) 2020-05-26
EP3621640A1 (de) 2020-03-18
AU2018265261A1 (en) 2019-12-05
CA3063051A1 (en) 2018-11-15
KR20220147684A (ko) 2022-11-03
KR102455340B1 (ko) 2022-10-18
US20210188947A1 (en) 2021-06-24
MX2019013370A (es) 2020-08-03
JP2023121765A (ja) 2023-08-31
JP2020519285A (ja) 2020-07-02
WO2018209055A1 (en) 2018-11-15
KR20200014780A (ko) 2020-02-11

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